Thesis (Ph.D.) - Cairo University - Faculty of Medicine - Department of Pharmacology

Introduction: This experimental study was done to investigate the role of empagliflozin in cardiac dysfunction induced in rats by three different models. Materials and methods: 64 male Sprague Dawley Albino rats were used in this study for 13 weeks and divided into 8 groups (n=8). 1A, 1B-Control groups where rats in 1A received 1ml saline daily by oral gavage for 8 weeks then in 1B treated with empagliflozin started from 8th week at dose of (10 mg/kg) daily by oral gavage for 5 weeks. Groups 2A&B, 3A&B were subjected to High Salt Diet (HSD), High Fat Diet group (HFD) for 8,7 weeks respectively then treated with empagliflozin in groups 2B, 3B daily for further 5 weeks. Group 4A&B were injected with Doxorubicin (DOX) intraperitoneally at weekly doses of 5 mg/kg for 5 weeks then treated with empagliflozin in group 4B for further 5 weeks. Body weight (BW), Systolic blood pressure (SBP), Electrocardiography (ECG), Echocardiography were recorded at the start, 8th week and at the end of the experiment. Heart /Body weight (HW/BW) ratio an index of cardiac hypertrophy was measured. At the end of the study, blood samples were taken for estimation of serum glucose, cholesterol, triglycerides and (BNP) levels. The isolated heart tissue was homogenized for estimation of (TNFÜ) and (MDA). Results: Empagliflozin showed dramatic effect in improving the cardiac dysfunction in the different models. It lowers BW in control & HFD treated groups, increased BW in DOX treated group, decreased blood pressure in control, HSD & HFD treated groups, decrease in HW/BW ratio in all groups. Moreover, The ECG ischemic changes were improved in HFD treated group and QT prolongation was prevented in DOX treated group with no changes observed in HSD treated group. Also, Empagliflozin resulted in significant improvement of systolic and diastolic function and prevention of the dilated cardiomyopathic effect noted in DOX treated group

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